Towards a future of scientific progress without the need for experimental animals: Global trends

Transcription

1 Towards a future of scientific progress without the need for experimental animals: Global trends Herman B.W.M.Koëter President, Alternatives Congress Trust

2 Towards a future of scientific progress without the need for experimental animals: Global trends Asian Congress 2016 and 29 th Annual meeting of the JSAAE November 2016, Karatsu & Fukuoka, Japan

3 The European Union, Norway,Switzerland, the UK, Canada and probably others abide by the principle: No experimental animals, unless... 3

4 The European Union, Norway,Switzerland, the UK, Canada and probably others abide by the principle: No experimental animals, unless... strictly necessary 4

5 ...we need them: To find out how our body and mind works; To prevent and cure us from nasty diseases; To avoid poisoning ourselves from toxic chemicals in our food, at our workplace, at home; Because we want our surgeons to be skilled when we need surgery; To learn how to avoid environmental disasters; etc, etc. 5

6 Main life science domains using experimental animals Fundamental research Translational and applied research Education and professional training purposes Regulatory and routine production testing 6

7 Main life science domains using experimental animals Fundamental research Translational and applied research Education and professional training purposes Regulatory and routine production testing 7

8 Regulatory and routine production testing quality control efficacy and tolerance testing toxicity testing risk assessment 8

9 Sold until 1910 without prescription! 9

10 Chemicals in our food Food and feed additives Food supplements Food preservatives Food contact materials Food processing aids Pesticide residues Veterinary drug residues GMO products Chemicals around us Chemical we are otherwise exposed to Industrial and workplace chemicals Household/cleaning chemicals Medicinal drugs Cosmetics and toiletries Chemical (air) pollutants Chemicals leaking from articles Plant protection products Total existing chemicals not adequately assessed > 3,000 > 35,000 10

11 Traditional regulatory risk assessment exposure Study A Study D Study B Study E hazard Risk Study C Study N 11

12 Traditional regulatory risk assessment exposure Study A Study D Study B Study E hazard Risk Study C Study N 12

13 Traditional regulatory risk assessment exposure Study A Study D Study B More than 20 endpoints Study E hazard Risk Study C Study N 13

14 Example of an average EU Pesticide Dossier 14

15 During the 80s and 90s: searching for reliable and relevant alternatives for specific animal tests: an exhaustive job Sensitisation (van Maximization or Bühler to Local Lymphnode assay (LLNA) Skin corrosion From LD50 to approximate acute toxicity Ex vivo eye irritation/corrosion tests Pyrogenicity test (fever response) 15

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17 25-29 years later 17

18 Traditional concept of replacement 18

19 History proved that focussing on alternatives for animal tests is deemed to failure

20 We are on the wrong track! 20

21 Fundamental changes in the current use of experimental animals will only be realised through profound alterations in the current approaches, technologies and policies 21

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23 Not only animal welfare concerns What was behind the requirement for specific toxicological tests? Is that situation still relevant? Has the gold standard for an acceptable risk ever been seriously evaluated and/or reconsidered? Could higher uncertainty and/or extrapolation factors be used to wave animal testing requirements? Is testing in humans negotiable/acceptable? Are we willing to accept a higher risk level if this would strongly reduce the use of experimental animals? 23

24 Not only animal welfare concerns Today Tomorrow highest level of safety acceptable level of risk 24

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26 Transition Hurdle hurdle 3 1 Starting with the most promising research domains (fundamental, applied, education, regulatory) 26

27 Selecting promising research Indicators (1): domains Possibility to define and fence off research domains; Research climate is constructive and aimed at innovative approaches; Already succesful 3R alternatives available 3R projects ongoing; Prepared to explore new tracks, rather than staying on beaten paths; 27

28 Selecting promising research Indicators (2): domains Available, accessible and possibly applicable technological innovations; Available and accessible Big Data banks, relevant for the research domain; No restrains for scientific developments; International support and cooperation expected. regulatory safety testing and risk assessment 28

29 Transition Hurdle hurdle 2 2 Problems cannot be solved at the same level of awareness that created them [Albert Einstein] Think outside the box 29

30 Transition hurdle 3 How can we achieve the original goal(s) without animal experiments? (e.g., chemically safe working environment) 30

31 New hazard assessment flow chart step 1 Purpose (e.g. systemic toxicity) Adequate non-animal assessment tools available? Yes, go to risk assessment 31

32 Use currently available non-animal tests/tools that should be accepted for regulatory risk assessment purposes Physical-chemical data Replacement tests for local effects (skin, eye) Replacement for pyrogenicity Replacement for acute oral, dermal and inhalation toxicity Replacement in vitro test for dermal absorption In vitro skin sensitization Mammalian erythrocyte micronucleus test 32

33 New hazard assessment flow chart Step 2 Purpose (e.g. systemic toxicity) Adequate non-animal assessment tools available? Adequate nonanimal hazard prediction tools available? Yes, go to risk assessment 33

34 Use currently available innovative non-animal hazard assessment tools and approaches High throughput prescreening tools Molecular toxicology for screening purposes Quantitative structure activity relationship (QSAR) Read-across predictions Adverse Outcome Pathways (AOP) Genomics assessment Organs on a chip / tissue and organ constructs Advanced stem cell technology Existing evidence based assessment Etcetera 34

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37 Hazard assessment flow chart Purpose (e.g. systemic toxicity) Step 3 Adequate non-animal assessment tools available? Adequate non-animal hazard prediction tools available? Big Data warehouse access Computational data analysis No reliable assessment possible? 37

38 Open access to all data at global level: Big data High-throughput chemical screening data (e.g., US.EPA ToxCast) Chemical exposure data and prediction models Computational (molecular) toxicity data, including genomics Systems biology data (holistic approach deciphering the complexity of organisms), High quality chemical structures and annotations data (EU ECHA data) QSAR -> 3D QSAR data bases Physical chemical properties databases (e.g., UNITAR, WHO) Database of chemicals listed by associated categories of chemical and product use Human Clinical Data (e.g., poison centers) Available toolboxes (e.g. OECD, LRI, Ambit) 38

39 Global dashboard

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45 Transition hurdle 4 Big Data analysis and evaluation The massive amount of data and subsequent interpretation require professional knowledge and skills which are most probably alien to the current risk assessment profession 45

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47 Global dashboard

48 Global dashboard

49 An example element of the global dashboard (launched 4 May 2016) Cefic launches AMBIT - a chemical safety prediction software

50 Hazard assessment flow chart Purpose (e.g. systemic toxicity) Step 4 Adequate non-animal assessment tools available? Adequate nonanimal hazard prediction tools available? Big Data warehouse access Computational data analysis Uncertainty factor, exposure estimate Reliable risk assessment 50

51 what next? From life science to computer science and back Smart information technologies for meta analyses Overall data interpretation and evaluation taking uncertainties into account From hazard to risk assessment (taking exposure in to account) Communication of the risk assessed Defining acceptable risk levels Transition: valorisation, familiarisation (parallel use) acceptance, globalisation 51

52 Acceptance and globalisation? At international level through a consensus building process at: EU level, OECD level, WHO/FAO (IPCS) level, ICH/VICH level, UN level Appropriate mindsets, willingness and perseverance 52

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54 A Chinese dream..to have an animal like a tool for biomedical discoveries Ji Weizhi, Director, Yunnan Key Laboratory of primate biomedical research (Nature, volume 532, 21 April, 2016) 54

55 Aim higher and wider Motto of the 11th World Scouts Jamboree, Marathon, Greece,